Altered Resting-state Cerebral Blood Flow And Functional Connectivity Associate With Major Depressive Disorder Patients With Suicidal Ideation

Background:Major depressive disorder(MDD)with continuous pathological processes and complex mechanisms has become a global public health problem.And suicidal ideation is a serious concomitish symptom and its causes are not prescribed.Clarifying the mechanisms of MDD with suicidal ideation and reducing the risk of suicide are to be urgently settled at the present time.The arterial spin labeling(ASL)can be used to assess brain functional changes by measuring abnormalities in cerebral blood flow(CBF)in vivo.At present,there are few studies focused on the resting-state cerebral perfusion and the seed-based functional connectivity(FC)alterations in MDD patients with suicidal ideation.The combination use of ASL and FC may help analyze the alteration of CBF and abnormal network patterns and explore the neuroimage characteristics of MDD patients with suicidal ideation.Further,integrating the CBF and FC approaches may reveal the potential mechanism underlying the suicidal ideation in the MDD patients at the cerebral blood perfusion and neural network level and provide new insight for sucidal prevention and treatment intervention.Objectives:At first,the aim of this neuroimaging study was to clarify the CBF alteration patterns in major depressive disorder with suicidal ideation and detect the correlations between CBF and behavioral performance;Second aim was to explore whether the brain regions with altered CBF also exhibited FC changes;At last,the study designed to explore whether the functional connectivity could mediate the association between CBF and behavioral scores.Methods:A total of 175 participants,including 47 MDD patients with non-suicidal ideation(MDD＿NSI),59 MDD patients with suicidal ideation(MDD＿SI)and 69healthy control(HC)subjects,were initially recruited into this study and underwent neuropsychological testing and MRI.The evaluation of MDD patients includes the Hamilton Depression Scale(HAMD)and the Hamilton Anxiety Scale(HAMA).All subjects underwent multi-mode MRI scans,including structural image,resting state and ASL perfusion imaging.Then the functional connectivity was based on the abnormal CBF seeds.We used one-way analysis of covariance and post hoc analysis to compare CBF and FC among the three groups.Partial correlation analyses were applied to detect the correlations between CBF,FC and behavioral scores.The medication analyses were conducted to investigate the association between CBF,FC and behavioral performance.Results:1)Compared with MDD＿NSI patients,MDD＿SI patients represented gradually increase in the HAMD-17,HAMD-cognition,and HAMD-sleep scores,and the significant difference were found between these two groups(P<0.05).2)Compared with HCs,the MDD＿NSI and MDD＿SI group exhibited increased CBF in the posterior cingulate cortex and decreased CBF in the bilateral visual cortex and bilateral striatum.The perfusion in the bilateral precuneus in MDD＿SI group are significantly increased than other two groups(P<0.05).3)The CBF in left visual cortex was positively correlated with HAMD-17(r~2=0.205,P=0.002),HAMD-anxiety(r~2=0.100,P=0.039),HAMD-retardation(r~2=0.124,P=0.020),HAMD-weight(r~2=0.176,P=0.005).The CBF in right visual cortex was positively correlated with HAMD-congnition(r~2=0.176,P=0.005).The CBF in left posterior cingulate cortex was positively correlated with HAMD-congnition(r~2=0.071,P=0.049)and HAMD-retardation(r~2=0.076,P=0.042),the CBF in right posterior cingulate cortex was positively correlated with HAMD-congnition(r~2=0.126,P=0.008)while the CBF in right posterior cingulate cortex was negatively correlated with HAMD-weight(r~2=0.098,P=0.020).4)Compared with the HCs,the two patient subgroups consistently showed reduced FC in the seed-based FC networks.The FC of left precuneus an-left middle temporal,right precuneus-right rostral anterior cingulate cortex,right precuneus-right inferior temporal gyrus,right posterior cingulate cortex-right fusiform area,right striatum-bilateral medial prefrontal cortex,right striatum-bilateral orbitofrontal cortex,right supplementary motor area-right orbitofrontal cortex,left insula-right lingual gyrus were increased relative to MDD＿NSI group.MDD＿SI patients showed a significant difference in FC between left visual cortex and right precental gyrus when compared with the MDD＿NSI and HC groups(P<0.05).5)There was no significant correlation between the altered FC and behavioral performance in the MDD＿NSI group,while there were wide correlations between the altered FC and behavioral performance in the MDD＿SI group.The FC of left supplementary motor area-right postcentral gyrus was positively correlated with HAMD-17(r~2=0.077,P=0.041).The FC of left posterior cingulate cortex-right middle temporal gyrus was positively correlated with HAMA(r~2=0.136,P=0.006).The FC of right striatum-bilateral medial prefrontal cortex was negatively correlated with HAMD-17(r~2=0.073,P=0.046).The FC of right striatum-bilateral medial prefrontal cortex was negatively correlated with HAMD-anxiety(r~2=0.093,P=0.023).The FC of left insula-left visual cortex was negatively correlated with HAMD-anxiety(r~2=0.082,P=0.034).The FC of left insula-right middle temporal gyrus was negatively correlated with HAMD-retardation(r~2=0.151,P=0.003).The FC of right precuneus-right dorsomedial prefrontal cortex was negatively correlated with HAMD-congnition(r~2=0.093,P=0.024).The FC of right precuneus-right rostral anterior cingulate cortex was negatively correlated with HAMD-retardation(r~2=0.100,P=0.019).The FC of left supplementary motor area-right orbitofrontal cortex was negatively correlated with HAMD-congnition(r~2=0.093,P=0.023).The FC of right striatum-bilateral medial prefrontal cortex was negatively correlated with HAMA(r~2=0.147,P=0.004).The FC of right precuneus-left middle temporal gyrus was negatively correlated with HAMA(r~2=0.108,P=0.015).The FC of right precuneus-right middle temporal gyrus was negatively correlated with HAMA(r~2=0.108,P=0.015).6)More importantly,the CBF-based abnormal FC mediated the association between CBF and behavioral performance in the MDD patients.Conclusion:Perfusion and brain network abnormalities are associated with MDD patients with suicidal ideation.The most prominent representation are the hypertransfusion in the bilateral precuneus and decreased FC in left visual cortex-right precentral gyrus in MDD patients with suicidal ideation.Importantly,the CBF-based abnormal FC could mediate the association between altered CBF and behavioral performance.